肌肉减少症
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摘要
肌肉减少症是一种肌肉量减少、肌肉强度下降、肌肉功能减退的综合征,在老年人、体力活动缺乏者、慢性疾病患者、恶性肿瘤患者中发病率较高,肌肉减少症患者跌倒、衰弱、失能的风险明显增加,独立生活能力减退,直接影响老年人生活质量和临床结局,早期认识肌肉减少症对延缓老年衰弱有积极意义。肌肉减少症原因可分为与年龄相关、营养相关、活动性相关、疾病相关这几个类型。年龄、内分泌改变、慢性炎症、恶液质、营养不良、维生素D缺乏等能引起肌肉减少症的发生。欧洲肌肉减少症工作组最新的专家共识建议使用低肌力作为肌肉减少症的最主要参数,推荐的诊断流程为:问卷筛查肌肉减少症高危人群-测量肌肉力量判断患病可能性-测量肌肉量确诊-测量躯体活动能力评估疾病严重程度。随着研究的进展人们对肌肉减少症的机制认识越来越清晰,早期营养干预、积极的抗阻运动及合理的药物治疗等可明显改善肌肉量和肌力,延缓老年人功能衰退,提高生活质量。随着老龄化的到来,人们对肌肉减少症的研究日益重视,发病机制日渐清晰,但药物治疗方面证据仍不足。
Sarcopenia is a syndrome associated with low muscle mass, muscle strength and physical performance. The morbidity rate of sarcopenia is pretty high in elderly people who are lake of physical activity, chronic disease patients and patients with malignancy. Patients have higher risks of falling, frailty and disability, and are more likely to be independence. Sarcopenia also impact on the quality of life and clinical outcome directly, and if we pay enough attention to sarcopenia early in life, it can help us delaying frailty. Sarcopenia are categorized as aged-related sarcopenia, sarcopenia with malnutrition, sarcopenia associated with activity, disease-related sarcopenia. Aging, endocrine changes, chronic inflammation, cachexia, malnutrition, vitamin D deficiency can lead to sarcopenia. The European Working Group on Sarcopenia in Older People revises their consensus recently, and recommends using muscle strength as the most important parameter of sarcopenia, and they updates its algorithm for sarcopenia casefinding, diagnosis and severity determination. Mechanism of sarcopenia has been realized within more and more studies developping.Nutrition supplement, resistance exercise and hormone replacement therapy can improve muscle mass and strength, delay function decline, improve quality of life. Etiology of sarcopenia is not integral yet, pharmacotherapy still needs more powerful evidence.
Sarcopenia is a syndrome associated with low muscle mass, muscle strength and physical performance. The morbidity rate of sarcopenia is pretty high in elderly people who are lake of physical activity, chronic disease patients and patients with malignancy. Patients have higher risks of falling, frailty and disability, and are more likely to be independence. Sarcopenia also impact on the quality of life and clinical outcome directly, and if we pay enough attention to sarcopenia early in life, it can help us delaying frailty. Sarcopenia are categorized as aged-related sarcopenia, sarcopenia with malnutrition, sarcopenia associated with activity, disease-related sarcopenia. Aging, endocrine changes, chronic inflammation, cachexia, malnutrition, vitamin D deficiency can lead to sarcopenia. The European Working Group on Sarcopenia in Older People revises their consensus recently, and recommends using muscle strength as the most important parameter of sarcopenia, and they updates its algorithm for sarcopenia casefinding, diagnosis and severity determination. Mechanism of sarcopenia has been realized within more and more studies developping.Nutrition supplement, resistance exercise and hormone replacement therapy can improve muscle mass and strength, delay function decline, improve quality of life. Etiology of sarcopenia is not integral yet, pharmacotherapy still needs more powerful evidence.
引文
1.Rosenberg IH. Sarcopenia:origins and clinical relevance. J Nutr.1997;127(5 Suppl):990S-991S.
2 .Han A, Bokshan SL, Marcaccio SE, et al. Diagnostic criteria and clinical outcomes in sarcopenia research:a literature review. J Clin Med. 2018;7(4).
3 .Garcia-Prat L, Martinez-Vicente M, Perdiguero E, et al. Autophagy maintains stemness by preventing senescence. Nature. 2016;529(7584):37-42.
4 .Frontera WR, Hughes VA, Fielding RA, et al. Aging of skeletal muscle:A 12-yr longitudinal study. J Appl Physiol(1985). 2000;88(4):1321-1326.
5 .Larsson L. Histochemical characteristics of human skeletal muscle during aging. Acta Physiol Scand. 1983;117(3):469-471.
6 .Rizzoli R, Reginster JY, Arnal JF, et al. Quality of life in sarcopenia and frailty. Calcif Tissue Int. 2013;93(2):101-120.
7 .Cruz-Jentoft AJ, Bahat G, Bauer J, et al. Sarcopenia:Revised European consensus on definition and diagnosis. Age Ageing. 2019;48(1):16-31.
8 .Chen LK, Liu LK, Woo J, et al. Sarcopenia in Asia:consensus report of the Asian Working Group for Sarcopenia. J Am Med Dir Assoc.2014;15(2):95-101.
9 .Chen LK, Lee WJ, Peng LN, et al. Recent advances in sarcopenia researchinasia:2016updatefromtheasianworkinggroupfor sarcopenia. J Am Med Dir Assoc. 2016;17(8):761-767.
10 . Cruz-Jentoft AJ, Landi F, Schneider SM, et al. Prevalence of and interventions for sarcopenia in ageing adults:A systematic review.ReportoftheInternationalSarcopeniaInitiative(EWGSOPand IWGS). Age Ageing. 2014;43(6):748-759.
11 . Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al. Sarcopenia:European consensus on definition and diagnosis:report of the European Working Group on Sarcopenia in Older People. Age Ageing. 2010;39(4):412-423.
12 . Hepple RT, Rice CL. Innervation and neuromuscular control in ageing skeletal muscle. J Physiol. 2016;594(8):1965-1978.
13 . TintignacLA,BrennerHR,RueggMA.Mechanismsregulating neuromuscular junction development and function and causesof muscle wasting. Physiol Rev. 2015;95(3):809-852.
14 .RudolfR,DeschenesMR,SandriM.Neuromuscularjunction degeneration in muscle wasting. Curr Opin Clin Nutr Metab Care.2016;19(3):177-181.
15 . Sandri M, Sandri C, Gilbert A, et al. Foxo transcription factors induce theatrophy-relatedubiquitinligaseatrogin-1andcauseskeletal muscle atrophy. Cell. 2004;117(3):399-412.
16 . Mammucari C, Milan G, Romanello V, et al. FoxO3 controls autophagy in skeletal muscle in vivo. Cell Metab. 2007;6(6):458-471.
17 . Fielding RA, Vellas B, Evans WJ, et al. Sarcopenia:An undiagnosed condition in older adults. Current consensus definition:prevalence,etiology, and consequences. International working group on sarcopenia. J Am Med Dir Assoc. 2011;12(4):249-256.
18 . Giovannini S, Marzetti E, Borst SE, et al. Modulation of GH/IGF-1axis:Potential strategies to counteract sarcopenia in older adults. Mech Ageing Dev. 2008;129(10):593-601.
19 . Brioche T, Kireev RA, Cuesta S, et al. Growth hormone replacement therapy prevents sarcopenia by a dual mechanism:Improvement of protein balance and of antioxidant defenses. J Gerontol A Biol Sci Med Sci. 2014;69(10):1186-1198.
20 . Salomon F, Cuneo RC, Hesp R, et al. The effects of treatment with recombinanthumangrowthhormoneonbodycompositionand metabolism in adults with growth hormone deficiency. N Engl J Med.1989;321(26):1797-1803.
21 .Rudman D, Kutner MH, Rogers CM, et al. Impaired growth hormone secretion in the adult population:Relation to age and adiposity. J Clin Invest.1981;67(5):1361-1369.
22 .BaumgartnerRN, WatersDL,GallagherD,etal.Predictorsof skeletal muscle mass in elderly men and women. Mech Ageing Dev.1999;107(2):123-136.
23 .MorleyJE,KaiserFE,PerryHR,etal.Longitudinalchangesin testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men. Metabolism. 1997;46(4):410-413.
24 . Messier V, Rabasa-Lhoret R, Barbat-Artigas S, et al. Menopause andsarcopenia:apotentialroleforsexhormones.Maturitas.2011;68(4):331-336.
25 .SorensenMB,Rosenfalck AM,HojgaardL,etal.Obesityand sarcopenia after menopause are reversed by sex hormone replacement therapy. Obes Res. 2001;9(10):622-626.
26 . Smith GI, Atherton P, Villareal DT, et al. Differences in muscle protein synthesis and anabolic signaling in the postabsorptive state and in responsetofoodin65-80yearoldmenandwomen.PLoSOne.2008;3(3):e1875.
27 . Hansen M. Female hormones:do they influence muscle and tendon protein metabolism? Proc Nutr Soc. 2018;77(1):32-41.
28 .MillerBF,HansenM,OlesenJL,etal.Noeffectofmenstrual cycleonmyofibrillarandconnectivetissueproteinsynthesisin contractingskeletalmuscle. AmJPhysiolEndocrinolMetab.2006;290(1):E163-E168.
29 .Kenny AM,PrestwoodKM,GrumanCA,etal.Effectsof transdermal testosterone on bone and muscle in older men with low bioavailabletestosteronelevels.JGerontol ABiolSciMedSci.2001;56(5):M266-M272.
30 .CleasbyME,JamiesonPM, AthertonPJ.Insulinresistanceand sarcopenia:mechanistic links between common co-morbidities. J Endocrinol. 2016;229(2):R67-R81.
31 . Rommel C, Bodine SC, Clarke BA, et al. Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways. Nat Cell Biol. 2001;3(11):1009-1013.
32 .MengSJ, YuLJ.Oxidativestress,molecularinflammationand sarcopenia. Int J Mol Sci. 2010;11(4):1509-1526.
33 . Katta A, Kundla S, Kakarla SK, et al. Impaired overload-induced hypertrophy is associated with diminished mTOR signaling in insulinresistant skeletal muscle of the obese Zucker rat. Am J Physiol Regul Integr Comp Physiol. 2010;299(6):R1666-R1675.
34 . Wang X, Hu Z, Hu J, et al. Insulin resistance accelerates muscle protein degradation:activation of the ubiquitin-proteasome pathway by defects in muscle cell signaling. Endocrinology. 2006;147(9):4160-4168.
35 . Srikanthan P, Karlamangla AS. Relative muscle mass is inversely associated with insulin resistance and prediabetes. Findings from the third National Health and Nutrition Examination Survey. J Clin Endocrinol Metab. 2011;96(9):2898-2903.
36 . Moon MK, Lee YJ, Choi SH, et al. Subclinical hypothyroidism has little influences on muscle mass or strength in elderly people. J Korean Med Sci. 2010;25(8):1176-1181.
37 .Beyer I, Mets T, Bautmans I. Chronic low-grade inflammation and agerelated sarcopenia. Curr Opin Clin Nutr Metab Care. 2012;15(1):12-22.
38 . Visser M, Pahor M, Taaffe DR, et al. Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women:The Health ABC Study. J Gerontol A Biol Sci Med Sci. 2002;57(5):M326-M332.
39 . Lieffers JR, Bathe OF, Fassbender K, et al. Sarcopenia is associated with postoperative infection and delayed recovery from colorectal cancer resection surgery. Br J Cancer. 2012;107(6):931-936.
40 . O'Toole PW, Jeffery IB. Gut microbiota and aging. Science. 2015;350(6265):1214-1215.
41 . Siddharth J, Chakrabarti A, Pannerec A, et al. Aging and sarcopenia associatewithspecificinteractionsbetweengutmicrobes,serum biomarkersandhostphysiologyinrats. Aging(AlbanyNY).2017;9(7):1698-1720.
42 . Bindels LB, Beck R, Schakman O, et al. Restoring specific lactobacilli levels decreases inflammation and muscle atrophymarkers in an acute leukemia mouse model. PLoS One. 2012;7(6):e37971.
43 . Bauer JM, Verlaan S, Bautmans I, et al. Effects of a vitamin D and leucine-enriched whey protein nutritional supplement on measures of sarcopenia in older adults, the PROVIDE study:a randomized, doubleblind, placebo-controlled trial. J Am Med Dir Assoc. 2015;16(9):740-747.
44 . Beaudart C, Buckinx F, Rabenda V, et al. The effects of vitamin D onskeletalmusclestrength,musclemass,andmusclepower:A systematic review and meta-analysis of randomized controlled trials. J Clin Endocrinol Metab. 2014;99(11):4336-4345.
45 . Visser M, Deeg DJ, Lips P. Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass(sarcopenia):The Longitudinal Aging Study Amsterdam. J Clin Endocrinol Metab. 2003;88(12):5766-5772.
46 . Wilkinson SB, Tarnopolsky MA, Macdonald MJ, et al. Consumption of fluid skim milk promotes greater muscle protein accretion after resistance exercise than does consumption of an isonitrogenous and isoenergetic soy-protein beverage. Am J Clin Nutr. 2007;85(4):1031-1040.
47 . Tieland M, van de Rest O, Dirks ML, et al. Protein supplementation improves physical performance in frail elderly people:a randomized,double-blind,placebo-controlledtrial.J AmMedDir Assoc.2012;13(8):720-726.
48 .缪琴,王蕾蕾,何芳,等.肠内营养制剂对肌肉衰减综合征患者肌力和肌含量的影响.全科医学临床与教育. 2016(05):499-502.
49 . Stipanuk MH. Leucine and protein synthesis:MTOR and beyond. Nutr Rev. 2007;65(3):122-129.
50 . Lozano-Montoya I, Correa-Perez A, Abraha I, et al. Nonpharmacological interventions to treat physical frailty and sarcopenia in older patients:A systematic overview-the SENATOR Project ONTOP Series. Clin Interv Aging. 2017;12:721-740.
51 . D'Souza RF, Marworth JF, Figueiredo VC, et al. Dose-dependent increases in p70S6K phosphorylation and intramuscular branchedchain amino acids in older men following resistance exercise and protein intake. Physiol Rep. 2014;2(8).
52 . Symons TB, Sheffield-Moore M, Wolfe RR, et al. A moderate serving of high-quality protein maximally stimulates skeletal muscle protein synthesis in young and elderly subjects. J Am Diet Assoc. 2009;109(9):1582-1586.
53 . Burd NA, Yang Y, Moore DR, et al. Greater stimulation of myofibrillar protein synthesis with ingestion of whey protein isolate v. Micellar casein at rest and after resistance exercise in elderly men. Br J Nutr.2012;108(6):958-962.
54 . Pennings B, Koopman R, Beelen M, et al. Exercising before protein intake allows for greater use of dietary protein-derived amino acids for de novo muscle protein synthesis in both young and elderly men. Am J Clin Nutr. 2011;93(2):322-331.
55 . Tessier AJ, Chevalier S. An update on protein, leucine, omega-3 fatty acids, and vitamin d in the prevention and treatment of sarcopenia and functional decline. Nutrients. 2018;10(8).
56 . Clark DJ, Patten C, Reid KF, et al. Muscle performance and physical function are associated with voluntary rate of neuromuscular activation in older adults. J Gerontol A Biol Sci Med Sci. 2011;66(1):115-121.
57 . Melov S, Tarnopolsky MA, Beckman K, et al. Resistance exercise reverses aging in human skeletal muscle. PLoS One. 2007;2(5):e465.
58 .HarridgeSD,Kryger A,Stensgaard A.Kneeextensorstrength,activation, and size in very elderly people following strength training.Muscle Nerve. 1999;22(7):831-839.
59 . Liao CD, Tsauo JY, Lin LF, et al. Effects of elastic resistance exercise on body composition and physical capacity in older women with sarcopenic obesity:A CONSORT-compliant prospective randomized controlled trial. Medicine(Baltimore). 2017;96(23):e7115.
60 . Galvao DA, Taaffe DR, Spry N, et al. Combined resistance and aerobic exercise program reverses muscle loss in men undergoing androgen suppression therapy for prostate cancer without bone metastases:A randomized controlled trial. J Clin Oncol. 2010;28(2):340-347.
61 . Johannsmeyer S, Candow DG, Brahms CM, et al. Effect of creatine supplementation and drop-set resistance training in untrainedaging adults. Exp Gerontol. 2016;83:112-119.
62 . Phillips SM. Nutritional supplements in support of resistance exercise to counter age-relatedsarcopenia. Adv Nutr. 2015;6(4):452-460.
63 . Salazar-Degracia A, Busquets S, Argiles JM, et al. Effects of the beta2agonistformoterolonatrophysignaling,autophagy,andmuscle phenotype in respiratory and limb muscles of rats with cancer-induced cachexia. Biochimie. 2018;149:79-91.
64 .GouspillouG,PicardM,GodinR,etal.Roleofperoxisome proliferator-activatedreceptorgammacoactivator1-alpha(PGC-1 alpha)in denervation-induced atrophy in aged muscle:Facts and hypotheses. Longev Healthspan. 2013;2(1):13.
65 . Yokokawa T, Kido K, Suga T, et al. Exercise training increases CISD family protein expression in murine skeletal muscle and white adipose tissue. Biochem Biophys Res Commun. 2018;506(3):571-577.
66 . Long DE, Peck BD, Martz JL, et al. Metformin to Augment Strength Training Effective Response in Seniors(MASTERS):study protocol for a randomized controlled trial. Trials. 2017;18(1):192.
67 . Band MM, Sumukadas D, Struthers AD, et al. Leucine and ACE inhibitors as therapies for sarcopenia(LACE trial):study protocol for a randomised controlled trial. Trials. 2018;19(1):6.
68. Lin CH, Yang H, Xue QL, et al. Losartan improves measures of activity, inflammation, and oxidative stress in older mice. Exp Gerontol. 2014;58:174-178.
2 .Han A, Bokshan SL, Marcaccio SE, et al. Diagnostic criteria and clinical outcomes in sarcopenia research:a literature review. J Clin Med. 2018;7(4).
3 .Garcia-Prat L, Martinez-Vicente M, Perdiguero E, et al. Autophagy maintains stemness by preventing senescence. Nature. 2016;529(7584):37-42.
4 .Frontera WR, Hughes VA, Fielding RA, et al. Aging of skeletal muscle:A 12-yr longitudinal study. J Appl Physiol(1985). 2000;88(4):1321-1326.
5 .Larsson L. Histochemical characteristics of human skeletal muscle during aging. Acta Physiol Scand. 1983;117(3):469-471.
6 .Rizzoli R, Reginster JY, Arnal JF, et al. Quality of life in sarcopenia and frailty. Calcif Tissue Int. 2013;93(2):101-120.
7 .Cruz-Jentoft AJ, Bahat G, Bauer J, et al. Sarcopenia:Revised European consensus on definition and diagnosis. Age Ageing. 2019;48(1):16-31.
8 .Chen LK, Liu LK, Woo J, et al. Sarcopenia in Asia:consensus report of the Asian Working Group for Sarcopenia. J Am Med Dir Assoc.2014;15(2):95-101.
9 .Chen LK, Lee WJ, Peng LN, et al. Recent advances in sarcopenia researchinasia:2016updatefromtheasianworkinggroupfor sarcopenia. J Am Med Dir Assoc. 2016;17(8):761-767.
10 . Cruz-Jentoft AJ, Landi F, Schneider SM, et al. Prevalence of and interventions for sarcopenia in ageing adults:A systematic review.ReportoftheInternationalSarcopeniaInitiative(EWGSOPand IWGS). Age Ageing. 2014;43(6):748-759.
11 . Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al. Sarcopenia:European consensus on definition and diagnosis:report of the European Working Group on Sarcopenia in Older People. Age Ageing. 2010;39(4):412-423.
12 . Hepple RT, Rice CL. Innervation and neuromuscular control in ageing skeletal muscle. J Physiol. 2016;594(8):1965-1978.
13 . TintignacLA,BrennerHR,RueggMA.Mechanismsregulating neuromuscular junction development and function and causesof muscle wasting. Physiol Rev. 2015;95(3):809-852.
14 .RudolfR,DeschenesMR,SandriM.Neuromuscularjunction degeneration in muscle wasting. Curr Opin Clin Nutr Metab Care.2016;19(3):177-181.
15 . Sandri M, Sandri C, Gilbert A, et al. Foxo transcription factors induce theatrophy-relatedubiquitinligaseatrogin-1andcauseskeletal muscle atrophy. Cell. 2004;117(3):399-412.
16 . Mammucari C, Milan G, Romanello V, et al. FoxO3 controls autophagy in skeletal muscle in vivo. Cell Metab. 2007;6(6):458-471.
17 . Fielding RA, Vellas B, Evans WJ, et al. Sarcopenia:An undiagnosed condition in older adults. Current consensus definition:prevalence,etiology, and consequences. International working group on sarcopenia. J Am Med Dir Assoc. 2011;12(4):249-256.
18 . Giovannini S, Marzetti E, Borst SE, et al. Modulation of GH/IGF-1axis:Potential strategies to counteract sarcopenia in older adults. Mech Ageing Dev. 2008;129(10):593-601.
19 . Brioche T, Kireev RA, Cuesta S, et al. Growth hormone replacement therapy prevents sarcopenia by a dual mechanism:Improvement of protein balance and of antioxidant defenses. J Gerontol A Biol Sci Med Sci. 2014;69(10):1186-1198.
20 . Salomon F, Cuneo RC, Hesp R, et al. The effects of treatment with recombinanthumangrowthhormoneonbodycompositionand metabolism in adults with growth hormone deficiency. N Engl J Med.1989;321(26):1797-1803.
21 .Rudman D, Kutner MH, Rogers CM, et al. Impaired growth hormone secretion in the adult population:Relation to age and adiposity. J Clin Invest.1981;67(5):1361-1369.
22 .BaumgartnerRN, WatersDL,GallagherD,etal.Predictorsof skeletal muscle mass in elderly men and women. Mech Ageing Dev.1999;107(2):123-136.
23 .MorleyJE,KaiserFE,PerryHR,etal.Longitudinalchangesin testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men. Metabolism. 1997;46(4):410-413.
24 . Messier V, Rabasa-Lhoret R, Barbat-Artigas S, et al. Menopause andsarcopenia:apotentialroleforsexhormones.Maturitas.2011;68(4):331-336.
25 .SorensenMB,Rosenfalck AM,HojgaardL,etal.Obesityand sarcopenia after menopause are reversed by sex hormone replacement therapy. Obes Res. 2001;9(10):622-626.
26 . Smith GI, Atherton P, Villareal DT, et al. Differences in muscle protein synthesis and anabolic signaling in the postabsorptive state and in responsetofoodin65-80yearoldmenandwomen.PLoSOne.2008;3(3):e1875.
27 . Hansen M. Female hormones:do they influence muscle and tendon protein metabolism? Proc Nutr Soc. 2018;77(1):32-41.
28 .MillerBF,HansenM,OlesenJL,etal.Noeffectofmenstrual cycleonmyofibrillarandconnectivetissueproteinsynthesisin contractingskeletalmuscle. AmJPhysiolEndocrinolMetab.2006;290(1):E163-E168.
29 .Kenny AM,PrestwoodKM,GrumanCA,etal.Effectsof transdermal testosterone on bone and muscle in older men with low bioavailabletestosteronelevels.JGerontol ABiolSciMedSci.2001;56(5):M266-M272.
30 .CleasbyME,JamiesonPM, AthertonPJ.Insulinresistanceand sarcopenia:mechanistic links between common co-morbidities. J Endocrinol. 2016;229(2):R67-R81.
31 . Rommel C, Bodine SC, Clarke BA, et al. Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways. Nat Cell Biol. 2001;3(11):1009-1013.
32 .MengSJ, YuLJ.Oxidativestress,molecularinflammationand sarcopenia. Int J Mol Sci. 2010;11(4):1509-1526.
33 . Katta A, Kundla S, Kakarla SK, et al. Impaired overload-induced hypertrophy is associated with diminished mTOR signaling in insulinresistant skeletal muscle of the obese Zucker rat. Am J Physiol Regul Integr Comp Physiol. 2010;299(6):R1666-R1675.
34 . Wang X, Hu Z, Hu J, et al. Insulin resistance accelerates muscle protein degradation:activation of the ubiquitin-proteasome pathway by defects in muscle cell signaling. Endocrinology. 2006;147(9):4160-4168.
35 . Srikanthan P, Karlamangla AS. Relative muscle mass is inversely associated with insulin resistance and prediabetes. Findings from the third National Health and Nutrition Examination Survey. J Clin Endocrinol Metab. 2011;96(9):2898-2903.
36 . Moon MK, Lee YJ, Choi SH, et al. Subclinical hypothyroidism has little influences on muscle mass or strength in elderly people. J Korean Med Sci. 2010;25(8):1176-1181.
37 .Beyer I, Mets T, Bautmans I. Chronic low-grade inflammation and agerelated sarcopenia. Curr Opin Clin Nutr Metab Care. 2012;15(1):12-22.
38 . Visser M, Pahor M, Taaffe DR, et al. Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women:The Health ABC Study. J Gerontol A Biol Sci Med Sci. 2002;57(5):M326-M332.
39 . Lieffers JR, Bathe OF, Fassbender K, et al. Sarcopenia is associated with postoperative infection and delayed recovery from colorectal cancer resection surgery. Br J Cancer. 2012;107(6):931-936.
40 . O'Toole PW, Jeffery IB. Gut microbiota and aging. Science. 2015;350(6265):1214-1215.
41 . Siddharth J, Chakrabarti A, Pannerec A, et al. Aging and sarcopenia associatewithspecificinteractionsbetweengutmicrobes,serum biomarkersandhostphysiologyinrats. Aging(AlbanyNY).2017;9(7):1698-1720.
42 . Bindels LB, Beck R, Schakman O, et al. Restoring specific lactobacilli levels decreases inflammation and muscle atrophymarkers in an acute leukemia mouse model. PLoS One. 2012;7(6):e37971.
43 . Bauer JM, Verlaan S, Bautmans I, et al. Effects of a vitamin D and leucine-enriched whey protein nutritional supplement on measures of sarcopenia in older adults, the PROVIDE study:a randomized, doubleblind, placebo-controlled trial. J Am Med Dir Assoc. 2015;16(9):740-747.
44 . Beaudart C, Buckinx F, Rabenda V, et al. The effects of vitamin D onskeletalmusclestrength,musclemass,andmusclepower:A systematic review and meta-analysis of randomized controlled trials. J Clin Endocrinol Metab. 2014;99(11):4336-4345.
45 . Visser M, Deeg DJ, Lips P. Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass(sarcopenia):The Longitudinal Aging Study Amsterdam. J Clin Endocrinol Metab. 2003;88(12):5766-5772.
46 . Wilkinson SB, Tarnopolsky MA, Macdonald MJ, et al. Consumption of fluid skim milk promotes greater muscle protein accretion after resistance exercise than does consumption of an isonitrogenous and isoenergetic soy-protein beverage. Am J Clin Nutr. 2007;85(4):1031-1040.
47 . Tieland M, van de Rest O, Dirks ML, et al. Protein supplementation improves physical performance in frail elderly people:a randomized,double-blind,placebo-controlledtrial.J AmMedDir Assoc.2012;13(8):720-726.
48 .缪琴,王蕾蕾,何芳,等.肠内营养制剂对肌肉衰减综合征患者肌力和肌含量的影响.全科医学临床与教育. 2016(05):499-502.
49 . Stipanuk MH. Leucine and protein synthesis:MTOR and beyond. Nutr Rev. 2007;65(3):122-129.
50 . Lozano-Montoya I, Correa-Perez A, Abraha I, et al. Nonpharmacological interventions to treat physical frailty and sarcopenia in older patients:A systematic overview-the SENATOR Project ONTOP Series. Clin Interv Aging. 2017;12:721-740.
51 . D'Souza RF, Marworth JF, Figueiredo VC, et al. Dose-dependent increases in p70S6K phosphorylation and intramuscular branchedchain amino acids in older men following resistance exercise and protein intake. Physiol Rep. 2014;2(8).
52 . Symons TB, Sheffield-Moore M, Wolfe RR, et al. A moderate serving of high-quality protein maximally stimulates skeletal muscle protein synthesis in young and elderly subjects. J Am Diet Assoc. 2009;109(9):1582-1586.
53 . Burd NA, Yang Y, Moore DR, et al. Greater stimulation of myofibrillar protein synthesis with ingestion of whey protein isolate v. Micellar casein at rest and after resistance exercise in elderly men. Br J Nutr.2012;108(6):958-962.
54 . Pennings B, Koopman R, Beelen M, et al. Exercising before protein intake allows for greater use of dietary protein-derived amino acids for de novo muscle protein synthesis in both young and elderly men. Am J Clin Nutr. 2011;93(2):322-331.
55 . Tessier AJ, Chevalier S. An update on protein, leucine, omega-3 fatty acids, and vitamin d in the prevention and treatment of sarcopenia and functional decline. Nutrients. 2018;10(8).
56 . Clark DJ, Patten C, Reid KF, et al. Muscle performance and physical function are associated with voluntary rate of neuromuscular activation in older adults. J Gerontol A Biol Sci Med Sci. 2011;66(1):115-121.
57 . Melov S, Tarnopolsky MA, Beckman K, et al. Resistance exercise reverses aging in human skeletal muscle. PLoS One. 2007;2(5):e465.
58 .HarridgeSD,Kryger A,Stensgaard A.Kneeextensorstrength,activation, and size in very elderly people following strength training.Muscle Nerve. 1999;22(7):831-839.
59 . Liao CD, Tsauo JY, Lin LF, et al. Effects of elastic resistance exercise on body composition and physical capacity in older women with sarcopenic obesity:A CONSORT-compliant prospective randomized controlled trial. Medicine(Baltimore). 2017;96(23):e7115.
60 . Galvao DA, Taaffe DR, Spry N, et al. Combined resistance and aerobic exercise program reverses muscle loss in men undergoing androgen suppression therapy for prostate cancer without bone metastases:A randomized controlled trial. J Clin Oncol. 2010;28(2):340-347.
61 . Johannsmeyer S, Candow DG, Brahms CM, et al. Effect of creatine supplementation and drop-set resistance training in untrainedaging adults. Exp Gerontol. 2016;83:112-119.
62 . Phillips SM. Nutritional supplements in support of resistance exercise to counter age-relatedsarcopenia. Adv Nutr. 2015;6(4):452-460.
63 . Salazar-Degracia A, Busquets S, Argiles JM, et al. Effects of the beta2agonistformoterolonatrophysignaling,autophagy,andmuscle phenotype in respiratory and limb muscles of rats with cancer-induced cachexia. Biochimie. 2018;149:79-91.
64 .GouspillouG,PicardM,GodinR,etal.Roleofperoxisome proliferator-activatedreceptorgammacoactivator1-alpha(PGC-1 alpha)in denervation-induced atrophy in aged muscle:Facts and hypotheses. Longev Healthspan. 2013;2(1):13.
65 . Yokokawa T, Kido K, Suga T, et al. Exercise training increases CISD family protein expression in murine skeletal muscle and white adipose tissue. Biochem Biophys Res Commun. 2018;506(3):571-577.
66 . Long DE, Peck BD, Martz JL, et al. Metformin to Augment Strength Training Effective Response in Seniors(MASTERS):study protocol for a randomized controlled trial. Trials. 2017;18(1):192.
67 . Band MM, Sumukadas D, Struthers AD, et al. Leucine and ACE inhibitors as therapies for sarcopenia(LACE trial):study protocol for a randomised controlled trial. Trials. 2018;19(1):6.
68. Lin CH, Yang H, Xue QL, et al. Losartan improves measures of activity, inflammation, and oxidative stress in older mice. Exp Gerontol. 2014;58:174-178.